Synthesis and Biological Evaluation of N-Heterocyclic Indolyl Glyoxylamides as Orally Active Anticancer Agents

Authors :: Li, W.-T.
Hwang, D.-R.
Chen, C.-P.
Shen, C.-W.
Huang, C.-L.
Chen, T.-W.
Lin, C.-H.
Chang, Y.-L.
Chang, Y.-Y.
Lo, Y.-K.
Tseng, H.-Y.
Lin, C.-C.
Song, J.-S.
Chen, H.-C.
Chen, S.-J.
Wu, S.-H.
Chen, C.-T.
Source :: Journal of Medicinal Chemistry; April 2003, Vol. 46 Issue: 9 p1706-1715, 10p
Publication Year :: 2003
Abstract: A series of N-heterocyclic indolyl glyoxylamides were synthesized and evaluated for in vitro and in vivo anticancer activities. They exhibited a broad spectrum of anticancer activity not only in murine leukemic cancer cells but also in human gastric, breast, and uterus cancer cells as well as their multidrug resistant sublines with a wide range of IC<INF>50</INF> values. They also induced apoptosis and caused DNA fragmentation in human gastric cancer cells. Among the compounds studied, <BO>7</BO> showed the most potent activity of growth inhibition (IC<INF>50</INF> = 17−1711 nM) in several human cancer cells. Given orally, compounds <BO>7</BO> and <BO>13</BO> dose-dependently prolonged the survival of animals inoculated with P388 leukemic cancer cells. N-Heterocyclic indolyl glyoxylamides may be useful as orally active chemotherapeutic agents against cancer and refractory cancerous diseases of multidrug resistance phenotype.

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